GCDR trial

JRCT ID: jRCTs051230119

Registered date:27/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: biliary tract cancer
• Date of first enrollment: 05/01/2024
• Target sample size: 38
• Study type: Interventional

Intervention(s)

1. First endoscopic RFA performed (Date performed = Day 0 of initial RFA.)
2. Start of GCD treatment
3. 2nd endoscopic RFA performed (2nd endoscopic RFA performed on day 84 of initial RFA.)
4. Resume GCD treatment (repeat up to a total of 8 cycles as GCD. Thereafter, durvalumab alone will be administered and study treatment will continue until study treatment discontinuation criteria are met)

Outcome(s)

• Primary Outcome: Percentage of serious adverse events

Secondary Outcome

Overall Survival
Progression-free survival
Overall response rate
Duration of stent patency
Incidence of GCD side effects (CTCAEver 5.0 Grade 3 or higher)
RFA complication rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients who are at least 18 years of age at the time consent is obtained.
(2) Patients with histologically confirmed unresectable advanced or metastatic adenocarcinoma of the biliary system, including extrahepatic bile duct cancer and gallbladder cancer. However, papillary carcinoma is excluded.
(3) Patients who have undergone biliary drainage for obstructive jaundice due to biliary adenocarcinoma and whose serum bilirubin after drainage is less than 2.0 times the upper limit of reference (ULN).
Note that patients with a confirmed diagnosis of Gilbert's syndrome are eligible regardless of the serum bilirubin level, if the biliary obstruction that is clinically problematic has been cleared by biliary drainage.
(4) Patients with an expected prognosis of at least 3 months.
(5) Patients who can undergo transpapillary RFA.
(6)Patients with unresectable or metastatic disease at the time of initial diagnosis are eligible if they have untreated disease.
(7)If surgery is performed for curative purposes, patients who relapse more than 6 months later and, if applicable, more than 6 months after completion of postoperative adjuvant therapy (chemotherapy and/or radiation therapy) are eligible.
(8)Patients with a World Health Organization (WHO)/ECOG PS of 0 or 1.
(9)Patients with one or more lesions identified as target lesions based on the new guidelines for determining response to treatment of solid tumors (RECIST), Version 1.1.
(10) Patients with no prior immunotherapy with other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, including but not limited to. However, anticancer vaccines used for therapeutic purposes are excluded.
(11) Patients with adequate organ function, bone marrow function, and coagulation capacity who meet the following conditions
Hemoglobin (9.0 g/dL and more)
Neutrophil count (1500/microliter and more)
Platelet count (100000/microliter and more)
ALT and AST 2.5 and less times the ULN. For patients with liver metastases, ALT and AST must be 5 and less times the ULN.
Patients with creatinine clearance more than 50 mL/min based on 24-hour urine collection or calculated by the Cockcroft-Gault formula below (using actual body weight).
Males: Ccr = (140 - age) x weight (kg)/72 x serum creatinine level (mg/dL)
Women: Ccr = 0.85 x (140 - age) x weight (kg)/{72 x serum creatinine level (mg/dL)
International normalized ratio (PT INR) 2.0 and less
(12) Body weight more than 30 kg.
(13) Patients who are capable of complying with the requirements and limitations described in the consent document and this study protocol, and who have signed the consent document in their own handwriting.

Exclude criteria

(1) Patients with ampullary tumors.
(2) Patients with Bismuth TYPE IV tumors or tumors located only in the intrahepatic bile duct.
(3) Patients with implanted cardiac pacemakers.
(4) Patients who have undergone Billroth II or Roux-en-Y reconstruction.
(5) Patients with a history of allogeneic organ transplantation.
(6) Patients with current or former autoimmune or inflammatory diseases (inflammatory bowel disease [e.g., colitis or Crohn's disease]), diverticulitis except diverticulosis, systemic lupus erythematosus, sarcoidosis syndrome or Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) ) in confirmed patients.
However, the following patients may be included.
Patients with vitiligo or alopecia.
Patients with hypothyroidism (e.g., after Hashimoto's disease) who are stable during hormone replacement therapy.
Patients with chronic skin diseases that do not require systemic treatment.
Patients with no active disease within 5 years prior to consent.
Patients with celiac disease controlled by diet alone.
(7) Patients with having such as uncured or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, uncontrolled arrhythmia, active interstitial lung disease (ILD), and severe chronic gastrointestinal disease with diarrhea.
(8) Patients with a history of another primary malignancy. However, the following are excluded.
Patients with malignancies that have been treated for curative purposes, have been inactive for at least 5 years prior to the start of treatment in this study, and have a low risk of recurrence.
Skin cancer other than melanoma or lentigo maligna that has been adequately treated and for which there is no evidence of disease.
Intraepithelial carcinoma that has been adequately treated and for which there is no evidence of disease.
(9) Patients with a history of soft meningeal carcinomatosis.
(10) Patients with a history of active primary immunodeficiency.
(11) Patients with active infectious diseases such as tuberculosis (TB confirmed by history, clinical evaluation including examination and radiological findings, and TB test) or human immunodeficiency virus (HIV 1/2 antibody positive).
(12) Patients who have not experienced resolution of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher toxicity (excluding alopecia, vitiligo, and laboratory tests specified in the selection criteria) attributable to prior anticancer therapy.
a.Patients who develop grade 2 or higher neuropathy will be evaluated individually in consultation with the study office.
b.Patients with irreversible toxicities that it is reasonable to expect will not be exacerbated by gemcitabine, cisplatin, or durvalumab will be eligible for inclusion only after consultation with the study office.
(13) Patients with brain metastases or spinal cord compression (including asymptomatic and appropriately treated disease). Patients with suspected brain metastases at screening should have an MRI (recommended) or CT scan of the brain performed prior to enrollment (both tests should be performed using intravenous contrast media).
(14) Patients with known allergy or hypersensitivity to gemcitabine, cisplatin, durvalumab, or their additives.
(15) Patients receiving any combination of chemotherapy, investigational therapy, biologic therapy, or hormonal therapy for the treatment of cancer. However, concomitant hormonal therapy for diseases unrelated to cancer (e.g., hormone replacement therapy) is permitted.
(16) Radiation therapy, including palliative radiation therapy, is not allowed prior to enrollment, except for radiation administered as adjuvant therapy after surgery.
(17)Patients who received attenuated live attenuated vaccine within 30 days prior to the first dose of study drug. Note that post-registration patients may not be vaccinated with live vaccine during the study drug administration period and for up to 90 days after the last dose of study drug.
(18) Patients who have undergone major surgery (as determined by the principal (sub)investigator) within 28 days prior to the first dose of study drug. Note that simple surgery of isolated lesions for palliation performed prior to 14 days prior to the first dose of study drug is acceptable.
(19) Patients currently using or who have used immunosuppressive drugs within 14 days prior to the first dose of study drug. However, the following are acceptable for inclusion.
Nasal, inhaled, or topical steroids or local steroid injections (e.g., intra-articular injections).
Physiologic doses of systemic corticosteroids not exceeding 10 mg/day of prednisone or equivalent.
Steroids as premedication for hypersensitivity reactions (e.g., premedication for CT scan).
(20) Patients who are enrolled in other clinical trials concurrently with the present study, unless they are in an observational (non-interventional) clinical trial or during the follow-up period of an interventional trial.
(21) Pregnant or lactating female patients, or fertile male or female patients who are unwilling to use an effective contraceptive method from screening until 90 days after the last dose.
(22) Patients with active HBV infection (hepatitis B).
(23)Patients who have been found to have active hepatitis C virus (HCV) infection with detectable hepatitis C virus (HCV) RNA levels in each of the performing medical laboratories. Note that patients with a positive hepatitis C (HCV) antibody test but no detectable HCV RNA will be eligible for inclusion.
(24) Patients who are unable to comply with the study procedures, limitations, and requirements and are determined by the principal investigator (subinvestigator) to be inappropriate to participate in the study.
(25) Patients who are determined by the principal (sub)investigator(s) to be ineligible to participate in the study.

Related Information

• Primary Sponsor: Kitano Masayuki
• Source(s) of Monetary Support: AstraZeneca K.K.